- Synthesis of MR-49, a deiodinated analog of tetraiodothyroacetic acid (tetrac), as a novel pro-angiogenesis modulator
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The tyrosine-based hormones 3,3′,5-triiodo-L-thyronine (L-T3) and L-thyroxine (L-T4) that are produced by the thyroid gland control metabolic functions. Iodothyronine deiodinase enzymes convert L-T4to L-T3, the form of thyroid hormone critical to genomic actions within cells and regulation of metabolism, and to reverse-L-T3, a hormone isoform that is largely inactive. We used tertiary amines in a study of deiodination based on derivatives of tetraiodothyroacetic acid (tetrac)—a naturally occurring derivative of L-T4—to mimic the action of the iodothyronine deiodinases and deiodination of the outer ring iodines. Deiodinated tetrac, MR-49, was found to be pro-angiogenic, with this activity exceeding that of L-T3and L-T4in a hemoglobin Matrigel plug assay of angiogenesis. Tetrac is anti-angiogenic via several nongenomic pathways, and the present studies of MR-49 reveal the critical contribution of outer ring iodines to the angiogenic properties of thyroid hormone analogues, which may have utility as pro-angiogenic pharmaceuticals.
- Rajabi, Mehdi,Sudha, Thangirala,Darwish, Noureldien H.E.,Davis, Paul J.,Mousa, Shaker A.
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p. 4112 - 4116
(2016/08/01)
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- SUBSTITUTED 4-PHENOXYPHENOL ANALOGS AS MODULATORS OF PROLIFERATING CELL NUCLEAR ANTIGEN ACTIVITY
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In one aspect, the invention relates to substituted 4-phenoxyphenol analogs, derivatives thereof, and related compounds,which are useful as inhibitors of proliferating cell nuclear antigen (PCNA); synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating hyperproliferative disorders associated with PCNA using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention
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- COMPOSITIONS OF DUAL THYROINTEGRIN ANTAGONISTS AND USE IN VASCULAR-ASSOCIATED DISORDERS
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A dual thyrointegrin antagonist and a method for treating an angiogenesis-mediated disorder and/or a hyperthyroidism disorders by introducing the dual thyrointegrin antagonist into animals (e.g., mammals, human beings). The dual thyrointegrin antagonist includes a chemical structure having a thyroid hormone antagonist and alphavbeta3 integrin antagonist in the same molecule
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- Design, synthesis, and biological evaluation of bifunctional thyrointegrin inhibitors: New anti-angiogenesis analogs
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Context: Inhibition of pathological angiogenesis. Objective: Obtaining new transactivator, bifunctional, thyroid antagonist, non-toxic anti-angiogenic compounds. Materials and methods: In silico drug design, synthesis in bulk and biological evaluation in chick chorioallantoic membrane (CAM) model. Results: Significant inhibition (range 6573%) at 0.252.0 g/ml doses. Discussion and conclusion: The synthesis of compounds (9), (10), and (11) incorporating long-chain moieties guanidine, urea, methyl amine and, propyl amine substitutions, respectively, into the core molecular framework of tetrac (tetraiodothyroacetic acid) were undertaken. The evaluation of the anti-angiogenic bioactivity of these compounds in the CAM model revealed no loss of activity in comparison with tetrac and XT199, which showed nearly 86% inhibition at dose levels of 1 and 0.5 g/ml, respectively, and validated the concept.
- Bridoux, Alexandre,Khan, Riaz A.,Chen, Celei,Cheve, Gwenael,Cui, Huadong,Dyskin, Evgeny,Yasri, Aziz,Mousa, Shaker A.
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p. 871 - 882
(2012/04/04)
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